M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
Phase I Clinical Trial of M6620 (VX-970, Berzosertib) in Combination With the Topoisomerase I Inhibitor Irinotecan in Patients With Advanced Solid Tumors
9 other identifiers
interventional
66
1 country
23
Brief Summary
This phase I trial studies the side effects and best dose of M6620 and irinotecan hydrochloride in treating patients with solid tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). M6620 and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2016
Longer than P75 for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 3, 2015
CompletedFirst Posted
Study publicly available on registry
November 4, 2015
CompletedStudy Start
First participant enrolled
July 22, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 7, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
March 6, 2027
ExpectedApril 13, 2026
March 1, 2026
6.6 years
November 3, 2015
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (MTD)
Will be defined as the highest dose level at which =\< 20% patients experience dose limiting toxicity. A logistic regression model will be used to determine the MTD using all patients.
Up to 28 days
Recommended phase 2 dose (RP2D) of ATR kinase inhibitor M6620 (VX-970, berzosertib) and irinotecan hydrochloride
The RP2D will be determined based on MTD and the feasibility of the administration.
Up to 28 days
Secondary Outcomes (6)
Incidence of adverse events of M6620 (VX-970, berzosertib) and irinotecan hydrochloride
Up to 6 months after completion of study treatment
Overall response rate
Up to 6 months after completion of study treatment
Incidence of stable disease
Up to 6 months after completion of study treatment
Progression-free survival
Duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up 6 months after completion of study treatment
Pharmacokinetic parameters of M6620 (VX-970, berzosertib) in combination with irinotecan hydrochloride
Days -14 through -11, 1, 2, and 15 through 18 of cycle 1 (each cycle = 28 days)
- +1 more secondary outcomes
Other Outcomes (1)
Change in biomarker levels
Baseline to up 6 months after completion of study treatment
Study Arms (1)
Treatment (irinotecan, M6620)
EXPERIMENTALPatients receive irinotecan hydrochloride IV over 90 minutes and M6620 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood samples throughout the study and undergo CT at screening, throughout the study, and during follow up.
Interventions
Given IV
Given IV
Correlative studies
Undergo CT
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed metastatic or unresectable malignancy that is refractory to standard therapy or for which no standard therapy exists and where irinotecan is deemed a reasonable treatment option
- FOR PATIENTS ENROLLED IN THE EXPANSION COHORT: Patients must have known deficiencies in the deoxyribonucleic acid (DNA)-Damage Response (DDR), e.g. mutations in ATM, PALB2, BRCA1/2 or other deficiencies after discussion with the Study Chair (prioritized), or patients can be enrolled with the following tumor types regardless of known DDR deficiency: pancreatic cancer, colorectal cancer, and small cell lung cancer
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1 cm) with spiral CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- No limit on prior lines of therapy for metastatic disease; prior adjuvant or neoadjuvant chemotherapy does not count as a prior line of therapy as long as completion of the adjuvant or neoadjuvant therapy was more than 1 year prior to patient enrollment
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of M6620 (VX-970, berzosertib) in combination with irinotecan in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky \>= 70%)
- Life expectancy of greater than 12 weeks
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (ULN); if liver involvement, =\< 5 x ULN
- Creatinine clearance \>= 60 mL/min/1.73 m\^2
- Patients must have archived tumor tissue from prior tumor biopsy or surgical resections available for submission that is sufficient to complete molecular profiling
- FOR PATIENTS ENROLLED IN THE EXPANSION COHORT: Willingness to undergo mandatory biopsies (day -13, approximately 18 to 22 hours post end of irinotecan infusion and day 2, approximately 18 to 22 hours post end of irinotecan infusion \[= 17 to 21 hours post end of M6620 (VX-970, berzosertib)\]); patients enrolled to this cohort should have tumors deemed easily accessible for biopsies with low likelihood of complication
- +3 more criteria
You may not qualify if:
- Patients who have had chemotherapy or other systemic therapy or radiotherapy or patients who have not recovered from adverse events due to prior administered agents as follows:
- Chemotherapy \< 4 weeks prior to entering the study
- Radiotherapy \< 4 weeks prior to entering the study
- Nitrosoureas/mitomycin C \< 6 weeks prior to entering the study
- Targeted therapy \< 2 weeks (or 5 half-lives, whichever is longer) prior to entering the study
- Those who have not recovered from clinically significant adverse events due to prior agents administered to grade =\< 1 or baseline, with exception of alopecia and peripheral neuropathy, unless approved by the protocol chair
- Immunotherapy \< 4 weeks prior to entering the study
- Patients who are receiving any other investigational agents
- Patients with unstable brain metastases should be excluded; however, patients with known brain metastases may participate in this clinical trial if they are clinically stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are on a stable or decreasing dose of steroids for at least 14 days prior to trial treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970, berzosertib) or irinotecan
- M6620 (VX-970, berzosertib) is primarily metabolized by CYP3A4; irinotecan and its active metabolite, SN-38, are metabolized by CYP3A4 and UGT1A1, respectively; therefore, concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; valproic acid is known to inhibit the process of glucuronidation and may potentially enhance the toxicity of irinotecan; medications that enhance glucuronidation (i.e. phenytoin, phenobarbital, carbamazepine, rifampin, etc.) may also enhance clearance of SN-38, which may possibly decrease efficacy; therefore, concomitant administration of these drugs should be avoided; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Uncontrolled intercurrent illness including, but not limited to, severe active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with chronic viral hepatitis may participate in this clinical trial if they are clinically stable with acceptable liver function
- Pregnant women are excluded from this study because M6620 (VX-970, berzosertib) as a DNA-damage response (DDR) inhibitor may have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970, berzosertib), breastfeeding should be discontinued if the mother is treated with M6620 (VX-970, berzosertib); these potential risks may also apply to other agents used in this study
- Human immunodeficiency virus (HIV)-positive patients with well-controlled disease, as determined by CD4 count and viral load, who are on antiretroviral therapy that does not contain a strong inducer or inhibitor of CYP3A4 (e.g. regimens containing ritonavir, cobicistat, efavirenz or etravirine) are allowed on trial; HIV-positive patients on combination antiretroviral therapy with strong inducers or inhibitors of CYP3A4 are ineligible because of the potential for pharmacokinetic interactions with M6620 (VX-970, berzosertib); patients with poorly controlled HIV are not eligible due to the increased risk of lethal infections when treated with marrow-suppressive therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
Keck Medical Center of USC Pasadena
Pasadena, California, 91105, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, 37204, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Liza C Villaruz
University of Pittsburgh Cancer Institute LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 3, 2015
First Posted
November 4, 2015
Study Start
July 22, 2016
Primary Completion
March 7, 2023
Study Completion (Estimated)
March 6, 2027
Last Updated
April 13, 2026
Record last verified: 2026-03